The metastatic dissemination of tumor cells within the circulation may involve platelets in transport of tumor cell emboli and in their attachment to the vessel wall. We have utilized the Baumgartner in vitro perfusion system to measure the interaction of cultured human tumor cells and of mixed tumor cell-platelet thrombi with subendothelial elements to evaluate the attachment phase and have used tumor cell-induced platelet aggregation to evaluate some of the factors which might affect transport in the circulation. We have shown that the platelet-tumor cell interaction can be effected by the thrombin-dependent and ADP-dependent mechanisms and that the requirement for Ca is greater in the former. Platelets from different individuals show different sensitivities to tumor cells. For the thrombin-dependent lines, the activation due to tissue factor present in microvesicles secreted by the tumor cells can induce coagulation, platelet aggregation, and thrombogenesis suggesting that intact cells may not be necessary for the induction of the hemostatic complications of malignancy. (A)